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The effects of autoantibodies against the second extracellular loop of α1-adrenoceptor on vasoconstriction

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Abstract

Recent studies have demonstrated the presence of autoantibodies against α1-adrenoceptor (α1-AAB) in the serum of patients with primary hypertension, and that these autoantibodies exert adrenergic-agonist-like effects. However, their role in the development of hypertension remains unclear. The current study determined whether α1-AAB can cause vascular contraction, and further investigated the cellular receptors that mediate their vasoactivity. Enzyme-linked immunosorbent assay (ELISA) was used to detect α1-AAB in blood samples collected from 73 patients with primary hypertension and 86 normotensive patients. IgGs were purified from mixed sera from 25 α1-AAB-positive hypertensive patients and 20 α1-AAB-negative normotensives, respectively. The vasoconstrictive effect of purified IgG from the sera of either hypertensive or normotensive patients was observed in isolated rat thoracic aorta, coronary artery, renal artery, middle cerebral artery, and mesenteric artery. The effects of α1-AAB administration on mean arterial blood pressure in vivo were also assessed. The frequency of α1-AAB presence was considerably higher in patients with primary hypertension than normotensive subjects (34.2 vs. 10.5%, P < 0.01). In isolated thoracic aortic rings, renal artery, middle cerebral artery, and coronary artery segments, α1-AAB induced vasoconstriction in a concentration-dependent fashion, which can be completely blocked by prazosin, a selective α1-adrenoceptor antagonist. The mean arterial pressure significantly increased after the administration of α1-AAB in vivo. Our results demonstrated that the α1-AAB (which exhibited remarkable effects of vascular contraction in vitro, elevated blood pressure in vivo, and showed no desensitization phenomena) may play a role in both elevating vascular resistance and the development and maintenance of hypertension.

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Acknowledgments

This research is supported in part by grants from NSFC (National Nature Science Foundation of People’s Republic of china, 30670835 to Huirong Liu, and NSFS (Nature Science Foundation of Shanxi province, 2006011106) to Huirong Liu.

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Authors and Affiliations

  1. Department of Physiology, Shanxi Medical University, 56 XinJian South Road, Taiyuan, Shanxi, People’s Republic of China

    Li Yan, Hong Yao, Jue Tian, Ye Wu, Guangzhao Yang & Huirong Liu

  2. State Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China

    Li Yan, Hong Yao, Jue Tian, Ye Wu & Huirong Liu

  3. Department of Biochemistry, Shanghai University of Chinese Traditional Medicine, Shanghai, People’s Republic of China

    Yanwu Xu

  4. Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China

    Wenxin Xue

  5. Department of Intensive Care Unit, Xishan Hospital, Taiyuan, Shanxi, People’s Republic of China

    Haiqiang Ren

  6. Department of Emergency Medicine, Jefferson Medical College, Thomas Jefferson University, 1020 Sansom Street, Philadelphia, PA, 19107-5004, USA

    Xin L. Ma

  7. Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, People’s Republic of China

    Huirong Liu

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  1. Li Yan
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  2. Yanwu Xu
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  3. Hong Yao
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  4. Wenxin Xue
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  5. Jue Tian
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  6. Haiqiang Ren
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  7. Ye Wu
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  8. Guangzhao Yang
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  9. Xin L. Ma
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  10. Huirong Liu
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Corresponding authors

Correspondence to Xin L. Ma or Huirong Liu.

Additional information

This research had partly been accepted for oral presentation at the Clinical Hypertension Sessions of AHA Scientific Sessions 2007 in 6 November 2007, Orlando, Florida.

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Yan, L., Xu, Y., Yao, H. et al. The effects of autoantibodies against the second extracellular loop of α1-adrenoceptor on vasoconstriction. Basic Res Cardiol 104, 581–589 (2009). https://doi.org/10.1007/s00395-009-0020-8

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  • DOI: https://doi.org/10.1007/s00395-009-0020-8

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